Testosterone levels in men are declining about 1% every year. In fact, the average testosterone tested in men have been decreasing about 1% per year since 1980s. It’s no doubt Diet, exercise, sleep and lifestyle play a major role in testosterone. Times have changed people work in offices instead of manual labor jobs. Diet isn’t exactly great now that the average person must go well out of their way to consume organic foods. Plastics and Mico plastics have been a contributor to lowering testosterone as well, and almost everything is covered, rapped or packaged in plastic. Testosterone affects our stamina, physical strength, adaptability to physical and mental stress, or so-called stress resistance. It is also responsible for sexual activity, sexual capabilities, and personal ambitions. It plays such a crucial role in our lives that levels of testosterone deviating from the norm effects our everyday life. Luckily modern science and medication provides solutions to this problem.
Briefly about testosterone
Testosterone is a steroid hormone that plays various physiological roles. Testosterone begins to be produced still in the womb at 9 weeks of pregnancy. This is when the male genitals are formed. Up to this point, boys do not differ from girls at all. In boys, testosterone begins to be actively produced at the age of 12 and by the age of 18 helps a young boy to transform into a man. In healthy adult men, testosterone production is regulated by the HPG axis. Higher cortical centers in the brain signal the hypothalamus to secrete gonadotropin-releasing hormone (GnRH) in a pulsatile fashion. GnRH, in turn, stimulates the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary which modulates testosterone production from the Leydig cells and spermatogenesis by the Sertoli cells, respectively. After 35-40 years, due to the natural age-related changes, the production of testosterone is reduced by 1-2% per year. However, there are many other reasons why a man’s testosterone can decrease this time: illness, injury, bad habits, stress, heredity, physical inactivity, obesity, environment, and irregular sex life.
In women, testosterone is produced by the ovaries and adrenal glands and is used (in the correct concentrations) as a basis for the formation of estrogens. In female organisms, testosterone may be increased after physical exercises and during pregnancy.
Deviation of testosterone level from the norm
Normal test results show total testosterone levels of:
• 270 to 1,070 ng/dL for men (depending on age)
• 15 to 70 ng/dL for women
The increased levels of testosterone may indicate premature puberty in males; adrenal hyperplasia in boys; adrenal gland tumors; extragonadal tumors that produce gonadotropin; gestational trophoblastic tumors; polycystic ovary syndrome (approximately 20% of all cases); testicular feminization syndrome; virilizing ovarian tumors; hirsutism.
A decrease in hormone level is characteristic of the following pathologies: autotoxicity syndrome with severe renal failure; liver failure; Down syndrome; myotonic dystrophy; cryptorchidism; primary and secondary hypogonadism; obesity in men; menopause in women; premature ovarian failure; delayed puberty in males.
Usually in the male body, low testosterone manifests as decreased or lack of libido; erectile dysfunction; decreased volume of seminal fluid at ejaculation; lack of or decreased pleasure from sex; lack of interest in life; rapid physical fatigue, and lack of energy. However, the causes of low levels are not just natural (internal cases). Stress, lack of calories and overeating, taking medication, overtraining, as well as illness, lack of sleep, and alcohol can affect testosterone levels.
In both cases (internal or external) men can increase natural testosterone on their own. If training, nutrition, and daily regimen don’t help, then medications come to the rescue, namely enclomiphene (EC).
What is EC
Enclomiphene is a relatively new medication that boosts testosterone in a natural way. It is more effective than the widely used clomiphene (clomid). Moreover, it allows to avoid a lot of side effects inherent to clomiphene. The fact is that clomiphene consists of two isomers: zuclomiphene (cis isomer) and enclomiphene (trans isomer). Zuclomiphene is an estrogen agonist, which is associated with a number of side effects, including pernicious effects on male fertility, while enclomiphene is anti-estrogenic in the same tissues.
How EC affects your body
The non-steroidal agent EC increases the release of gonadotropin-dependent testosterone from the testes. EC acts as a selective estrogen receptor modulator, exerting an antagonistic effect on the hypothalamus. This effect ultimately leads to increased gonadotropin secretion and subsequent stimulation of testosterone production. In other words, having a positive stimulating effect on gonadotropins’ production, it suppresses estrogen in tissues and increases the production of endogenous testosterone.
Exogenous testosterone administration (injections, patches, pellets, or gels) diminishes sperm production because of the decreased intra-testicular concentration of testosterone and suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Suppression of FSH release from the pituitary gland impairs sperm production and suppression of LH release inhibits intra-testicular testosterone production. According to the results of clinical studies, EC has a clearly positive effect on the release or synthesis of LH and FSH from the pituitary possibly through the hypothalamus.
EC effect
• consistently increases testosterone levels
• increases gonadotropin levels
• has no effect on spermatogenesis
• increases total motile sperm count
Safety studies
According to the studies, it takes enclomiphene roughly two weeks for it to build up in your system and for you to begin seeing positive results (testosterone level and sperm counts increase almost twice). Overall, enclomiphene is very safe. No evidence of toxicity was found in safety studies of enclomiphene. The most common side effects are increased libido, acne, and potentially a temper. More rarely, headache, nausea, diarrhea, and dizziness have been reported. EC is well tolerated and the frequency of side effects does not differ significantly from placebo. No interactions with other medications have been reported.
How long to take EC
EC is safe and effective for long-term management. According to the experts, the effects on LH and total testosterone persisted for at least 1 week (elimination half-life of EC is 10 hours) after stopping treatment.
In the end
• Enclomiphene is effective in ameliorating testosterone deficiency and maintaining semen quality
• It is a safe and effective therapy for men who desire to maintain future potential fertility
• In older men, enclomiphene could be used as monotherapy, particularly if the risk of testosterone therapy seems to be too high for specific patients
Works Cited
- Kim ED, McCullough A, Kaminetsky J: Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: Restoration instead of replacement. BJU Int. 2016, 117:677-85. 10.1111/bju.13337
- Kaminetsky J, Werner M, Fontenot G, Wiehle RD: Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: Comparison with testosterone gel. J Sex Med. 2013, 10:1628-35. 10.1111/jsm.12116
- Khodamoradi K, Khosravizadeh Z, Parmar M, Kuchakulla M, Ramasamy R, Arora H: Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: Current and future prospects. F S Rev. 2021, 2:32-42. 10.1016/j.xfnr.2020.11.001
- Thomas J, Suarez Arbelaez M, Narasimman M, et al. (July 06, 2023) Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study. Cureus 15(7): e41476. doi:10.7759/cureus.41476
- Patel AS, Leong JY, Ramos L, Ramasamy R. Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility. World J Mens Health. 2019 Jan;37(1):45-54. https://doi.org/10.5534/wjmh.180036
- Ronald Wiehle, Glenn R Cunningham, Nelly Pitteloud, Jenny Wike, Kuang Hsu, Gregory K Fontenot, Michele Rosner, Andrew Dwyer, Joseph Podolski. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study. BJU Int. 2013 Dec; 112(8): 1188–1200. Published online 2013 Nov 4. doi: 10.1111/bju.12363
- https://www.fda.gov/media/159043/download
- Earl JA, Kim ED. Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism. Expert Rev Endocrinol Metab. 2019 May;14(3):157-165. doi: 10.1080/17446651.2019.1612239. Epub 2019 May 7. PMID: 31063005.
- Ronald D. Wiehle, Gregory K. Fontenot, Michael S. Willett, Wilfredo D. Garcia, Joseph S. Podolski. Enclomiphene Citrate Stimulates Serum Testosterone in Men With Low Testosterone Within 14 Days. Journal of Men’s Health.Dec 2014.196-205.https://doi.org/10.1089/jomh.2014.0006
- Rodriguez KM, Pastuszak AW, Lipshultz LI. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016 Aug;17(11):1561-7. doi: 10.1080/14656566.2016.1204294. Epub 2016 Jul 4. PMID: 27337642; PMCID: PMC5009465.
